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121.
Haejin Yoon Seung-Hyun ShinDong Hoon Shin Yang-Sook ChunJong-Wan Park 《Biochemical and biophysical research communications》2014
Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) determine cancer cell fate under hypoxia. Despite the similarities of their structures, HIF-1α and HIF-2α have distinct roles in cancer growth under hypoxia, that is, HIF-1α induces growth arrest whereas HIF-2α promotes cell growth. Recently, sirtuin 1 (Sirt1) was reported to fine-tune cellular responses to hypoxia by deacetylating HIF-1α and HIF-2α. Yet, the roles of Sirt1 in HIF-1α and HIF-2α functions have been controversial. We here investigated the precise roles of Sirt1 in HIF-1α and HIF-2α regulations. Immunological analyses revealed that HIF-1α K674 and HIF-2α K741 are acetylated by PCAF and CBP, respectively, but are deacetylated commonly by Sirt1. In the Gal4 reporter systems, Sirt1 was found to repress HIF-1α activity constantly in ten cancer cell-lines but to regulate HIF-2α activity cell type-dependently. Moreover, Sirt1 determined cell growth under hypoxia depending on HIF-1α and HIF-2α. Under hypoxia, Sirt1 promoted cell proliferation of HepG2, in which Sirt1 differentially regulates HIF-1α and HIF-2α. In contrast, such an effect of Sirt1 was not shown in HCT116, in which Sirt1 inactivates both HIF-1α and HIF-2α because conflicting actions of HIF-1α and HIF-2α on cell growth may be offset. Our results provide a better understanding of the roles of Sirt1 in HIF-mediated hypoxic responses and also a basic concept for developing anticancer strategy targeting Sirt1. 相似文献
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123.
Soohwan Yum Huijeong ParkSungchae Hong Seongkeun JeongWooseong Kim Yunjin Jung 《Biochemical and biophysical research communications》2014
We investigated anti-colitic effects of N-(2-mercaptopropionyl)-glycine (NMPG), a diffusible antioxidant, in TNBS-induced rat colitis model and a potential molecular mechanism underlying the pharmacologic effect of the antioxidant. NMPG alleviated colonic injury and effectively lowered myeloperoxidase activity. Moreover, NMPG substantially attenuated expression of pro-inflammatory mediators in the inflamed colon. NMPG induced hypoxia-inducible factor-1α (HIF-1α) in human colon carcinoma cells, leading to elevated secretion of vascular endothelial growth factor (VEGF), a target gene product of HIF-1 involved in ulcer healing of gastrointestinal mucosa. NMPG induction of HIF-1α occurred by inhibiting HIF prolyl hydroxylase-2 (HPH-2), an enzyme that plays a major role in negatively regulating HIF-1α protein stability. In in vitro Von Hippel-Lindau protein binding assay, the inhibitory effect of NMPG on HPH-2 was attenuated by escalating dose of ascorbate but not 2-ketoglutarate, cofactors of the enzyme. Consistent with this, cell-permeable ascorbate significantly attenuated NMPG induction of HIF-1α in cells. Our data suggest that NMPG is an anti-colitic antioxidant that exerts its pharmacologic effects at least partly through activation of an ulcer healing pathway, HIF-1-VEGF. 相似文献
124.
Jolanta Szenajch Gabriel Wcislo Jee-Yeong Jeong Cezary Szczylik Laurie Feldman 《生物化学与生物物理学报:癌评论》2010
Recombinant human erythropoietin (rhEPO) has been used clinically to alleviate cancer- and chemotherapy-related anemia. However, recent clinical trials have reported that rhEPO also may adversely impact disease progression and survival. The expression of functional EPO receptors (EPOR) has been demonstrated in many human cancer cells where, at least in vitro, rhEPO can stimulate cell growth and survival and may induce resistance to selected therapies. 相似文献
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127.
Zhongcai Ma Kenny Y.C. Kwong David Paek 《Biochemical and biophysical research communications》2010,400(4):569-574
Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at −158 to −153 bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation. 相似文献
128.
Deng Li Qingfeng He Tao Kang Huan Yin Xian Jin Weiqiong Gan Jingjing Hu Lifei Peng 《Biochemical and biophysical research communications》2010,392(2):155-159
Factor VIIa-tissue factor complex (fVIIa/TF) and factor XIa (fXIa) play important roles in the initiation and amplification of coagulation, respectively. They may be good targets for the development of novel anticoagulants to treat and prevent thromboembolic disease. In this study, we cloned, expressed and identified a novel anticoagulant peptide, AcaNAP10, from the blood-feeding nematode Ancylostoma caninum. AcaNAP10 showed potent anticoagulant activity and doubled the activated partial thromboplastin and prothrombin times at estimated concentrations of 92.9 nM and 28.8 nM, respectively. AcaNAP10 demonstrated distinct mechanisms of action compared with known anticoagulants. It inhibited fXIa and fVIIa/TF with IC50 values of 25.76 ± 1.06 nM and 123.9 ± 1.71 nM, respectively. This is the first report on an anticoagulant that can inhibit both fXIa and fVIIa/TF. This anticoagulant peptide may be an alternative molecule for the development of novel anticoagulants. 相似文献
129.
Ariel Alonso Annouschka Laenen Geert Molenberghs Helena Geys Tony Vangeneugden 《Biometrics》2010,66(4):1061-1068
Summary The reliability of multi‐item scales has received a lot of attention in the psychometric literature, where a myriad of measures like the Cronbach's α or the Spearman–Brown formula have been proposed. Most of these measures, however, are based on very restrictive models that apply only to unidimensional instruments. In this article, we introduce two measures to quantify the reliability of multi‐item scales based on a more general model. We show that they capture two different aspects of the reliability problem and satisfy a minimum set of intuitive properties. The relevance and complementary value of the measures is studied and earlier approaches are placed in a broader theoretical framework. Finally, we apply them to investigate the reliability of the Positive and Negative Syndrome Scale, a rating scale for the assessment of the severity of schizophrenia. 相似文献
130.
TROY N. TOLLEFSON LISA A. SHIPLEY WOODROW L. MYERS DUANE H. KEISLER NAIRANJANA DASGUPTA 《The Journal of wildlife management》2010,74(5):974-986
ABSTRACT Recent work suggests that availability and quality of forage in late summer and early autumn, a time when female ungulates face multiple energetic demands, is critical to reproduction in wild ungulates. Therefore, we examined direct links between nutritional quality of diets, body condition, and reproduction of lactating mule deer. Using captive mule deer, we tested the hypothesis that females consuming diets with lower digestible energy (DE; kJ/g) would have lower DE intake rates (DEI; MJ/day), have less body fat and muscle, have later estrus cycles, and have lower pregnancy and twinning rates. Deer fed lower DE diets had lower DEI during summer and autumn. In turn, deer with lower DEI, regardless of diet DE, had lower body mass, body fat, and muscle thickness. When nutritional quality of diets began to decline earlier in the summer, relationships between food quality, DEI, and body condition were stronger. Although DEI did not influence estrus date for deer that became pregnant before 21 December, deer with lower DEI had a lower probability of becoming pregnant and had a lower probability of producing twins. Measures of body condition in October (i.e., body mass, body fat, and muscle depth) predicted pregnancy and twinning rates in mule deer. Serum concentration of hormones leptin and Insulin Growth Factor 1 were not good predictors of body condition or reproduction. These findings suggest that managers concerned with productivity of mule deer populations should consider focusing on assessing and improving quality of forage available in summer and autumn. 相似文献